Ms. Imrit Noi, M. Sc. candidate
Department of materials science and engineering,Technion
Technion City, Haifa 3200003, Israel firstname.lastname@example.org
same time, it remains a big challenge due to the complex structure of the mucus, the viscoelastic layer formed by highly crosslinked mucin fibers that covers all the exposed epithelial tissues not covered by skin, which might preclude drug permeability. The engineering of drug nanocarriers that combine fine-tuned mucoadhesive and mucopenetrating features is currently being investigated to ensure a more efficient mucosal delivery of the active agents. Mucoadhesion is essential to prolong its residence time in mucosa. Thiolated polymers are relatively new family of materials that display thiol pendant chain groups and have emerged as one of the most versatile approaches to confermucoadhesiveness. Conversely, mucopenetration entails the facilitation of the nanocarrier passage across it. Recently, a combination of N-acetyl cysteine (NAC) moieties with poly(ethylene glycol) (PEG) has been reported to increase the penetration of nanoparticles across mucus. Our research group developed a new family of amphiphilic nanogels based on the non-covalent crosslinking of polymeric micelles (PMs)[3,4]. Following this conceptual line, here we report on the synthesis and characterization of mucoadhesive/mucopenetrating nanocarriers produced by the ionotropic crosslinking of chitosan-g-poly(methyl methacrylate) (CS-g-PMMA) PMs that were surface-modified with two types of thiol residues, namely NAC and 3-mercaptopropionic acid (3MPA). We successfully conjugated 3% and 0.5% w/w of NAC and 3MPA, respectively (determined by Ellman’s assay). The critical micellar concentration was in the 0.03-0.06% w/v range, as measured by dynamic light scattering. PMs ionotropically crosslinked with tripolyphosphate showed very good cell compatibility (Caco2 and HT29-MTX cell lines) in 0.05%-0.1% w/v range after 4-48 h. Finally, the permeability was characterized in an in vitro model of the intestinal epithelium based on the co-culture of Caco-2/HT29-MTX.
 Bernkop-Schnürch A. Adv Drug Deliv Rev 57 (2005) 1569-1582.
 Suk JS et al. Nanomedicine 6 (2011) 365-375.
 Raskin MM et al., Nanomedicine 11 (2016) 217-233.
 Moshe H et al., Biomater Sci (2017), in press.